489 research outputs found

    The boundary cap: a source of neural crest stem cells that generate multiple sensory neuron subtypes

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    The boundary cap (BC) is a transient neural crest-derived group of cells located at the dorsal root entry zone (DREZ) that have been shown to differentiate into sensory neurons and glia in vivo. We find that when placed in culture, BC cells self-renew, show multipotency in clonal cultures and express neural crest stem cell (NCSCs) markers. Unlike sciatic nerve NCSCs, the BC-NCSC (bNCSCs) generates sensory neurons upon differentiation. The bNCSCs constitute a common source of cells for functionally diverse types of neurons, as a single bNCSC can give rise to several types of nociceptive and thermoreceptive sensory neurons. Our data suggests that BC cells comprise a source of multipotent sensory specified stem cells that persist throughout embryogenesis

    Fluvio-deltaic avulsions during relative sea-level fall.

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    Understanding river response to changes in relative sea level (RSL) is essential for predicting fluvial stratigraphy and source-to-sink dynamics. Recent theoretical work has suggested that rivers can remain aggradational during RSL fall, but field data are needed to verify this response and investigate sediment deposition processes. We show with field work and modeling that fluvio-deltaic systems can remain aggradational or at grade during RSL fall, leading to superelevation and continuation of delta lobe avulsions. The field site is the Goose River, Newfoundland-Labrador, Canada, which has experienced steady RSL fall of around 3ā€“4 mm yrā»Ā¹ in the past 5 k.y. from post-glacial isostatic rebound. Elevation analysis and optically stimulated luminescence dating suggest that the Goose River avulsed and deposited three delta lobes during RSL fall. Simulation results from Delft3D software show that if the characteristic fluvial response time is longer than the duration of RSL fall, then fluvial systems remain aggradational or at grade, and continue to avulse during RSL fall due to superelevation. Intriguingly, we find that avulsions become more frequent at faster rates of RSL fall, provided the system response time remains longer than the duration of RSL fall. This work suggests that RSL fall rate may influence the architecture of falling-stage or forced regression deposits by controlling the number of deposited delta lobes

    Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals

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    Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat) or inactivated (e.g., cow and sheep) in some species but retained in others (e.g., human, horse, and pig). Likewise, many species (e.g., human, chimpanzee, cow, and sheep) retain the GnRHR2 gene but lack the appropriate coding sequence to produce a full-length protein due to gene coding errors; although production of GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene (e.g., mouse) or most exons entirely (e.g., rat). In contrast, old world monkeys, musk shrews, and pigs maintain the coding sequence required to produce a functional GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor that interacts with GĪ±q/11 to mediate cell signaling. However, GnRHR2 retains a cytoplas-mic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor in mammals has been elusive, likely because common laboratory models lack both the ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the interaction between nutritional status and sexual behavior in the female brain. Within peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. In the female, GnRH2 and its receptor may help mediate placental function, implanta-tion, and ovarian steroidogenesis. Furthermore, both the GnRH2 and GnRHR2 genes are expressed in human reproductive tumors and represent emerging targets for cancer treatment. Thus, GnRH2 and GnRHR2 have diverse functions in mammals which remain largely unexplored

    Expression and Role of Gonadotropin-Releasing Hormone 2 and Its Receptor in Mammals

    Get PDF
    Gonadotropin-releasing hormone 1 (GnRH1) and its receptor (GnRHR1) drive mammalian reproduction via regulation of the gonadotropins. Yet, a second form of GnRH (GnRH2) and its receptor (GnRHR2) also exist in mammals. GnRH2 has been completely conserved throughout 500 million years of evolution, signifying high selection pressure and a critical biological role. However, the GnRH2 gene is absent (e.g., rat) or inactivated (e.g., cow and sheep) in some species but retained in others (e.g., human, horse, and pig). Likewise, many species (e.g., human, chimpanzee, cow, and sheep) retain the GnRHR2 gene but lack the appropriate coding sequence to produce a full-length protein due to gene coding errors; although production of GnRHR2 in humans remains controversial. Certain mammals lack the GnRHR2 gene (e.g., mouse) or most exons entirely (e.g., rat). In contrast, old world monkeys, musk shrews, and pigs maintain the coding sequence required to produce a functional GnRHR2. Like GnRHR1, GnRHR2 is a 7-transmembrane, G protein-coupled receptor that interacts with GĪ±q/11 to mediate cell signaling. However, GnRHR2 retains a cytoplas-mic tail and is only 40% homologous to GnRHR1. A role for GnRH2 and its receptor in mammals has been elusive, likely because common laboratory models lack both the ligand and receptor. Uniquely, both GnRH2 and GnRHR2 are ubiquitously expressed; transcript levels are abundant in peripheral tissues and scarcely found in regions of the brain associated with gonadotropin secretion, suggesting a divergent role from GnRH1/GnRHR1. Indeed, GnRH2 and its receptor are not physiological modulators of gonadotropin secretion in mammals. Instead, GnRH2 and GnRHR2 coordinate the interaction between nutritional status and sexual behavior in the female brain. Within peripheral tissues, GnRH2 and its receptor are novel regulators of reproductive organs. GnRH2 and GnRHR2 directly stimulate steroidogenesis within the porcine testis. In the female, GnRH2 and its receptor may help mediate placental function, implanta-tion, and ovarian steroidogenesis. Furthermore, both the GnRH2 and GnRHR2 genes are expressed in human reproductive tumors and represent emerging targets for cancer treatment. Thus, GnRH2 and GnRHR2 have diverse functions in mammals which remain largely unexplored

    Erratum: Divergent activity of the gonadotropin-releasing hormone receptor gene promoter among genetic lines of pigs is partially conferred by nuclear factor (NF)- kB, specificity protein (SP)1-like and GATA-4 binding sites

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    BACKGROUND: Binding of gonadotropin-releasing hormone (GnRH) to its receptor (GnRHR) on gonadotropes within the anterior pituitary gland is essential to reproduction. In pigs, the GnRHR gene is also located near a genetic marker for ovulation rate, a primary determinant of prolificacy. We hypothesized that pituitary expression of the GnRHR gene is alternatively regulated in genetic strains with elevated ovulation rates (Chinese Meishan and Nebraska Index) vs. standard white crossbred swine (Control). METHODS: Luciferase reporter vectors containing 5118 bp of GnRHR gene promoter from either the Control, Index or Meishan swine lines were generated. Transient transfection of line-specific, full length, deletion and mutation constructs into gonadotrope-derived Ī±T3-1 cells were performed to compare promoter activity and identify regions necessary for divergent regulation of the porcine GnRHR gene. Additionally, transcription factors that bind the GnRHR promoter from each line were identified with electrophoretic mobility shift assays (EMSA). RESULTS: Dramatic differences in luciferase activity among Control, Index and Meishan promoters (19-, 27- and 49-fold over promoterless control, respectively; Pā€‰\u3cā€‰0.05) were established. A single bp substitution (-1690) within a previously identified upstream enhancer (-1779/-1667) bound GATA-4 in the Meishan promoter and the p52/p65 subunits of nuclear factor (NF)-ĪŗB in the homologous Control/Index promoters. Transient transfection of vectors containing block replacement mutations of either the GATA-4 or NF-ĪŗB binding sites within the context of their native promoters resulted in a 50 and 60 % reduction of luciferase activity, respectively (Pā€‰\u3cā€‰0.05). Furthermore, two single-bp substitutions in the Meishan compared to Control/Index promoters resulted in binding of the p52 and p65 subunits of NF-ĪŗB and a specificity protein 1 (SP1)-like factor (-1235) as well as GATA-4 (-845). Vectors containing the full-length Meishan promoter harboring individual mutations spanning these regions reduced luciferase activity by 25 and 20 %, respectively, compared to native sequence (Pā€‰\u3cā€‰0.05). CONCLUSIONS: Elevated activity of the Meishan GnRHR gene promoter over Control/Index promoters in Ī±T3-1 cells is partially due to three single nucleotide polymorphisms resulting in the unique binding of GATA-4 (-1690), the p52/p65 subunits of NF-kB in combination with a SP1-like factor (-1235), and GATA-4 (-845)

    Variation in carbon footprint of milk due to management differences between Swedish dairy farms

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    To identify mitigation options to reduce greenhouse gas (GHG) emissions from milk production (i.e. the carbon footprint (CF) of milk), this study examined the variation in GHG emissions among dairy farms using data from previous CF studies on Swedish milk. Variation between farms in these production data, which were found to have a strong influence on milk CF were obtained from existing databases of e.g. 1051 dairy farms in Sweden in 2005. Monte Carlo analysis was used to analyse the impact of variations in seven important parameters on milk CF concerning milk yield (energy corrected milk (ECM) produced and delivered), feed dry matter intake (DMI), enteric methane emissions, N content in feed DMI, N-fertiliser rate and diesel used on farm. The largest between farm variation among the analysed production data were N-fertiliser rate (kg/ha) and diesel used (l/ha) on farm (coefficient of variation (CV) 31-38%). For the parameters concerning milk yield and feed DMI the CV was approx. 11 and 8%, respectively. The smallest variation in production data was found for N content in feed DMI. According to the Monte Carlo analysis, these variations in production data led to a variation in milk CF of between 0.94 and 1.33 kg CO2 equivalents (CO2e) per kg ECM, with an average value of 1.13 kg/CO2e kg ECM. We consider that this variation of Ā±17% that was found based on the used farm data would be even greater if all Swedish dairy farms were included, as the sample of farms in this study was not totally unbiased. The variation identified in milk CF indicates that a potential exists to reduce GHG emissions from milk production on both national and farm level through changes in management. As milk yield and feed DMI are two of the most influential parameters for milk CF, feed conversion efficiency (i.e. units ECM produced per unit DMI) can be used as a rough key performance indicator for predicting CF reductions. However, it must be borne in mind that feeds have different CF due to where and how they are produced

    A transgenic pig model expressing a CMV-ZsGreen1 reporter across an extensive array of tissues.

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    Since genetic engineering of pigs can benefit both biomedicine and agriculture, selecting a suitable gene promoter is critically important. The cytomegalovirus (CMV) promoter, which can robustly drive ubiquitous transgene expression, is commonly used at present, yet recent reports suggest tissue-specific activity in the pig. The objective of this study was to quantify ZsGreen1 protein (in lieu of CMV promoter activity) in tissues from pigs harboring a CMV-ZsGreen1 transgene with a single integration site. Tissue samples

    Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns

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    Exosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans. Here, we assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescue Drosha homozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs

    Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns

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    Exosomes participate in cell-to-cell communication, facilitated by the transfer of RNAs, proteins and lipids from donor to recipient cells. Exosomes and their RNA cargos do not exclusively originate from endogenous synthesis but may also be obtained from dietary sources such as the inter-species transfer of exosomes and RNAs in bovine milk to humans. Here, we assessed the bioavailability and distribution of exosomes and their microRNA cargos from bovine, porcine and murine milk within and across species boundaries. Milk exosomes labeled with fluorophores or fluorescent fusion proteins accumulated in liver, spleen and brain following suckling, oral gavage and intravenous administration in mice and pigs. When synthetic, fluorophore-labeled microRNAs were transfected into bovine milk exosomes and administered to mice, distinct species of microRNAs demonstrated unique distribution profiles and accumulated in intestinal mucosa, spleen, liver, heart or brain. Administration of bovine milk exosomes failed to rescue Drosha homozygous knockout mice, presumably due to low bioavailability or lack of essential microRNAs

    Extending an industrial root controller : implementation and applications of a fast open sensor interface

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    An overview is given of the design and implementation of a platform for fast external sensor integration in an industrial robot system called ABB S4CPlus. As an application and motivating example, the implementation of force-controlled grinding and deburring within the AUTOFETT-project is discussed. Experiences from industrial usage of the fully developed prototype confirms the appropriateness of the design choices, thus also confirming the fact that control and software need to be tightly integrated. The new sensor can be used for the prototyping and development of a wide variety of new application
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